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Sleep Deprived? Mind your dopamine.

The views expressed are those of the author and are not necessarily those of Scientific American.


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Most of us will suffer sleep deprivation at one time or another. I’m not talking our usual state of broken sleep, 5 hours a night, or something else. I’m talking a full night without sleep, the kind many people experience in the army, with a brand new (or not so brand new) baby, or more frivolously (I hope), in college.

We all know what sleep deprivation does to us. We’re unable to pay attention. We’re often cold or hot. We can’t think straight, we start doing very strange things (you would not BELIEVE the crazy dances I’ve made up…), and of course, we’re really, really tired.

But why do these symptoms happening? What’s going on in the brain during sleep deprivation to explain this behavior? Well, in part, it might be changes in your D2 receptors.


(Source)

Volkow et al. “Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatumin the Human Brain” Journal of Neuroscience, 2012.

There are lots of signs that point toward the involvement of the neurotransmitter dopamine in wakefulness. Drugs that increase levels of dopamine in brain (including, but not limited to, drugs like cocaine, amphetamine, meth, and Ritalin) also increase feelings of wakefulness. Increasing dopamine in the brain via genetic alterations, like getting rid of the dopamine transporter in a mouse, stopping dopamine from getting recycled, produces a mouse that sleeps less. Diseases that are characterized by low dopamine levels, like Parkinsons, also have daytime sleepiness.

But a neurotransmitter is only as good as its receptor. Dopamine has two main types of receptors, and the current hypothesis is that the wakefulness promoting effects of dopamine may be controlled partially by the D2 type receptor. Antipsychotics, which block D2 type receptors, make people sleepy, and previous studies showed decreased D2 binding in the brains of sleep deprived people. But the question is: what is causing the decreases in D2 when people are sleep deprived? The authors of this study hypothesized that this was due to increased dopamine release, which would cause decreases in D2 receptors (this is a basic idea in pharmacology, when a group of receptors is overstimulated, some receptors will leave the membrane, making the membrane less sensitive to stimulation).

To test this hypothesis, they took a bunch of human volunteers, and either sleep deprived them overnight (they kept them in a facility with a nurse bugging them to keep their eyes open if they got drowsy), or kept them in the facility to get a good night’s rest (all participants underwent both conditions). In the morning, they looked at the D2 receptors in the striatum of the brain, an area with loads of dopamine and associated with things like arousal and reward. To do this, they used positron emission tomography (PET), which uses a radioactive tracer (C-raclopride), which binds to D2 type receptors, allowing you to see how many are present.

They showed that D2 type receptor binding was definitely lower in sleep deprived people. But what does this mean? Does it mean that there’s more dopamine release when you’re tired, decreasing the D2 type receptors? Or do the D2 type receptors decrease for some other reason? To look at this, the authors of the study treated the participants with methylphenidate (Ritalin), which increased the amounts of dopamine. They hypothesized that if sleep deprivation produced more dopamine release, the methylphenidate should produce larger increases in dopamine than in well rested patients.

Above you can see nice pretty pictures showing places where the methylphenidate produced larger or smaller changes in sleep deprived patients vs not…but overall there was no difference.

This means that the decrease in D2 type receptors that the authors see with sleep deprivation is NOT due to increases in DA release during sleep deprivation. They confirmed this with studies in rats, and showed that the sleep deprived rats showed no increases in dopamine, but showed similar D2 type receptor changes.

So what is going on? Unfortunately, the authors didn’t go after that question, though they talk about a “different physiological mechanism”. They do hypothesize that adenosine might have something to do with it. Adenosine is a neurochemical which you know best from your morning cup of coffee. Caffeine increases wakefulness by antagonizing adenosine receptors, and adenosine itself promotes sleepiness. Not only that, one of the areas involved in this effect appears to be the striatum, the dopamine-rich area the authors were looking at in this study. Caffeine can increase D2 type receptor levels in this area. So it seems like the next thing to look at would be how adenosine and dopamine might be interacting following sleep deprivation (though unfortunately, they didn’t look at it here).

So what does this mean? Well, the changes in D2 type receptors could help explain some of the other changes in behavior that come with sleep deprivation, changes like increases in risk taking behavior, impulsivity, and drug relapse. These are all things which increase when people are sleep deprived. So the changes seen in D2 type receptors could help explain show these behavioral changes occur. But while we see changes in receptors, we still don’t know why, and the proposed mechanism still needs to be tested.

Volkow, N., Tomasi, D., Wang, G., Telang, F., Fowler, J., Logan, J., Benveniste, H., Kim, R., Thanos, P., & Ferre, S. (2012). Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain Journal of Neuroscience, 32 (19), 6711-6717 DOI: 10.1523/JNEUROSCI.0045-12.2012

Scicurious About the Author: Scicurious is a PhD in Physiology, and is currently a postdoc in biomedical research. She loves the brain. And so should you. Follow on Twitter @Scicurious.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. tom1245 1:42 pm 02/18/2014

    Hi,

    I don’t understand the statement about Ritalin.

    -
    Today I took my Ritalin later in the day. Before that, I was very awake/happy and moving around and switching from one thing to another OK but mainly also even did stuff, OK; around 40 Minutes after I took my Ritalin I stopped running around doing things in the house and sat down and just sat down and made a mind map of what I have to do today, and then how I would do that.

    40 Minutes after I took my Ritalin:
    - I was more calm. (LESS awake)
    - I did not move around as much.
    - I stayed on task.
    - Mainly, really I was the same, but I felt more control of myself and was just more calm and mild.

    Generally, like what I’m just trying to say, like to the editors maybe, just go easy with the Ritalin-hating and how some editors on silly news websites say its speed and all that, because like really. Even before I was on Ritalin I felt very fast and speedy and just other things also (Note: -> I ate proper diet, exercised , etc). Now, if I take the Ritalin it stops me feeling very fast and all that.

    so like, just please think more? or just… really.

    thank you.

    like of course, you do what you do of course 100% but just don’t be thinking its speed or something because I can assure you it sure as hell is not.

    Link to this
  2. 2. Vivamagonline 8:47 am 09/22/2014

    Natural Calm’s newest spokesperson Sitara Hewitt talks about why magnesium supplements are the key to keeping her stress in check, and how simple rituals, healthy eating and a little exercise make her busy life manageable.

    By Bonnie Siegler

    After a kiss and cuddle with her four-year-old son, Sitara Hewitt starts her day by saying positive affirmations. “Miracles will happen.” “It’s going to be a great day.” Then she heads downstairs for a green smoothie. The Canadian actor, who has homes in both Toronto and Los Angeles, needs a regular morning ritual to level out her hectic days. She’s found that it’s the little things that can make the difference between chaos and calm.

    Link to this
  3. 3. Vivamagonline 8:48 am 09/22/2014

    Natural Calm’s newest spokesperson Sitara Hewitt talks about why magnesium supplements are the key to keeping her stress in check, and how simple rituals, healthy eating and a little exercise make her busy life manageable.

    By Bonnie Siegler

    After a kiss and cuddle with her four-year-old son, Sitara Hewitt starts her day by saying positive affirmations. “Miracles will happen.” “It’s going to be a great day.” Then she heads downstairs for a green smoothie. The Canadian actor, who has homes in both Toronto and Los Angeles, needs a regular morning ritual to level out her hectic days. She’s found that it’s the little things that can make the difference between chaos and calm.

    - See more at: http://www.vivamagonline.com/calm-amidst-the-hollywood-storm/#sthash.snx96KL2.dpuf

    Link to this

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